Chronic wounds are difficult to heal spontaneously largely due to the corrupted extracellular matrix (ECM) where cell ingrowth is obstructed. Thus, the objective of this study was to develop a three-dimensional (3D) biodegradable scaffold mimicking native ECM to replace the missing or dysfunctional ECM, which may be an essential strategy for wound healing. The 3D fibrous scaffolds of poly(lactic acid-co-glycolic acid) (PLGA) were successfully fabricated by liquid-collecting electrospinning, with 5 similar to 20 mu m interconnected pores. Surface modification with the native ECM component aims at providing biological recognition for cell growth. Human dermal fibroblasts (HDFs) successfully infiltrated into scaffolds at a depth of similar to 1400 mu m after seven days of culturing, and showed significant progressive proliferation on scaffolds immobilized with collagen type I. In vivo models showed that chronic wounds treated with scaffolds had a faster healing rate. These results indicate that the 3D fibrous scaffolds may be a potential wound dressing for chronic wound repair.